Project Summary: Age-related hearing deficits are a prevalent public health problem, and major knowledge gaps remain in our understanding of the underlying central neural mechanisms. The long-term goal of our research is to understand how aging and hearing loss affects organization of central auditory pathways concurrent with peripheral degeneration, and how these changes contribute to hearing difficulties. The central hypothesis of the proposed research is that neuromodulatory feedback pathways become dysregulated with age, particularly the olivocochlear (OC) efferents, reducing the aging brain's capacity to protect against peripheral damage and compensate for diminished peripheral input. In younger adults, OC neurons protect against damaging sounds, enhance processing of acoustic transients in noise, and enhance auditory selective attention. These processes are disrupted in aging listeners, and dysfunction of the OC system is likely a contributing factor. The primary objectives of the proposed research are to investigate age-related changes in the organization and function of the OC pathways, define their effects on the quality of the afferent sensory signals sent back to the brain, and reveal how these changes contribute to age-related auditory deficits. A secondary goal is to understand how genetic and environmental manipulation of OC neurons can be leveraged to protect against age-related auditory deficits. We will pursue these goals with three Specific Aims 1) Quantify age-related changes in OC neuronal morphology and their relationship to cochlear afferent degeneration and hearing in noise; 2) Quantify age-related changes in the OC efferent-modulated sensory signal received and processed by the auditory brainstem; 3) Determine the protective effects of genetic and environmental manipulations to increase OC system activation against age-related hearing deficits. Our approach will integrate multiple techniques to understand the relationship between the olivocochlear system and age-related hearing decline, including the auditory brainstem response, single unit physiology, behavior, and quantitative anatomical analysis of peripheral and central components of OC neurons in aging mouse models. These studies will lead to a better understanding of age-related changes in brain-controlled modulation of sensory function. In the future, these pathways may be manipulated to protect against age-related hearing decline and improve hearing in the presence of competing sounds.